LLM Abstracts Supplement
Authors: Hina Khan, Jafry Rabab, Rios Adan, Stein Anthony, Lavrencic Mojca, Garciaz Sylvain, Huls Gerwin, Maiti Abhishek, Boissel Nicolas, Botton Stephane, Fleming Shaun, Zwaan Michel, David Leeuw, Desai 10, Arellano Martha, Avigan David, Langemeijer Saskia, Jensen Kyle, Wagenaar Timothy, Mi Gu, Abbadessa Giovanni, Bajel Ashish, Shah Dhruvil, Kochhar Smriti, Plenn Eion, Mcinnis Curtis, Benson Christopher, Jain Rohit, Desai Krishna, Kakakarla Madhulika, Iqbal Sabah, Pereira Kristal, Rather Manzoor, Thirumaran Rajesh, Leyfman Yan, Helena Coloma, Van Kieft, Joshi Muskan, Gayathri Menon, Balasubramanian Maduri, Azeez Ahmed, Keira Smith, Elizabeth Heller, Chorya Harshal, Alves Gabrielle, Abbas Rabab, Ghazal Jenna, Nadar Soumiya, Wilson Steve, Grivna Shane, Park Chandler
Journal: American Journal of Hematology (2023)

Introduction/Background/Significance: Acute undifferentiated leukemia (AUL) is a rare, aggressive leukemia lacking expression of lineage-specific markers.Diagnostic and therapeutic challenges include differentiating AUL from acute leukemias of ambiguous lineage (ALALs).The diagnosis of AUL is made once comprehensive immunophenotyping, cytogenetics, and molecular genomics exclude any lineage-specific leukemia.Materials and Methods/Case Presentation/Objective: A 56-year-old woman presented with easy bruising, petechial rash, and fevers for 2 weeks.Laboratory tests revealed a hemoglobin of 8.5 g/dL, WBC 8.1 K WBC/μL, and platelets of 5,000 platelets/μL.Serum LDH was mildly elevated at 288 U/L.Peripheral blood smear showed increased blasts.Bone marrow aspirate and biopsy showed 75% blasts that expressed no specific lineage markers.Cytogenetics were normal, and molecular findings revealed the presence of an IDH1 mutation.A diagnosis of AUL was confirmed.The patient was treated with FLAG-IDA (fludarabine 30 mg/m 2 x 5 days, cytarabine 1.5 g/m 2 x 5 days, idarubicin 8 mg/m 2 x 3 days, and G-CSF with tbo-filgastrim 480 μg from day 1 x 7 days).Her induction course was complicated by neutropenic fever and sepsis requiring intravenous antibiotics.A bone marrow from day 23 of treatment revealed a complete response with incomplete hematologic recovery.The patient was referred for allogenic hematopoietic stem cell transplantation (HSCT).Results/Description/Main Outcome Measure: ALALs are extremely rare hematologic malignancies, accounting for < 4% of all leukemias.AUL is a subset of ALAL defined by the absence of any immunophenotypic lineagespecific markers and of acute myeloid leukemia (AML)-or acute lymphoblastic leukemia (ALL)-defining cytogenetics.AUL has a higher incidence in older patients, with a median age of onset of 74 years.Based on a retrospective analysis of 1888 patients with AUL, median overall survival if chemotherapy was administered was 13 months (95% CI, 11-15 months) versus 1 month if no treatment was delivered.There is no standard of care treatment for AUL, although most reported cases received AML induction regimens rather than ALL regimens.In a retrospective study of 54 cases of ALALs (of which 24 assigned to AUL based on WHO 2016 classification), all but 2 patients received AML treatment regimens, including 54% of patients who received standard 7+3 (7 days of cytarabine and 3 days of anthracycline-based therapy), 11% of patients who received hypomethylating agents, and supportive care for the remaining 35% of patients.In a review of outcomes of 8 patients with AUL after allogenic HSCT, median overall survival at 1 year was 37.5% (95% CI, 9.9%-65.9%). Conclusion:AUL is a rare hematological malignancy with a decreasing incidence over time due to improved diagnostics and classification.Optimal treatment is unclear given the lack of lineage markers, with most reported cases utilizing AML-based treatments.Outcomes remain poor in AUL.Our case highlights an example of AUL for which the FLAG-IDA regimen was utilized with achievement of a complete response with incomplete hematologic recovery after cycle 1 of induction.The patient was subsequently referred for allogenic HSCT and achieved a prolonged remission of >1 year duration.